PHILADELPHIA â€” The cancer-causing form of the gene Myc alters the metabolism of mitochondria, the cellâ€™s powerhouse, making it dependent on the amino acid glutamine for survival. In fact, 40 percent of all â€śhard-to-treatâ€ť cancers have a mutation in the Myc gene.

The findings appear in this weekâ€™s issue of Cancer Cell. Simon is also a professor of Cell and Developmental Biology at the Perelman School of Medicine, University of Pennsylvania. The Penn team collaborated with colleagues from The Childrenâ€™s Hospital of Philadelphia (CHOP) John Maris and Michael Hogarty.

"These findings come from studies of fundamental cellular pathways and would not have been discovered without ongoing support for basic research,â€ť notes Simon. â€śTranslational research is very important, but equal emphasis on basic research of processes such as cellular metabolism is critical for the ultimate cure of cancer.â€ť

Glutamine depletion in Myc-mutant cells induces cell death through a complicated series of molecular switches involving the three protein executors and the DNA-binding protein ATF4. Knowing this, the team showed that either agonists of ATF4 or inhibitors of glutamine metabolism potently caused cell death in assays using neuroblastoma cells and inhibited tumor growth in transgenic mice. Drugs in these two classes have been approved by the Food and Drug Administration and are being tested in clinical trials for other disorders.

Multimedia

A leader in the rapidly changing field of epigenetics, Shelley L. Berger has built a world-class epigenetics program at Penn that she says is distinguished by the diverse and relevant expertise of the science faculty associated with it.

Penn students in the course, Living World in Archaeological Science, offered in the Penn Museumâ€™s Center for the Analysis of Archaeological Materials (CAAM), have learned about scientific analysis of skeletal rem

Drawing from the seemingly disparate fields of economics, electrical engineering, and computer science, Rakesh Vohraâ€™s work requires the support of an institution resolutely committed to interdisciplinary researchâ€”a level of commitment he says few institutions beyond Penn have.